Tooth mineral is composed predominantly of calcium hydroxyapatite, Ca10(PO4)6(OH)2, which may be partially substituted with anions such as carbonate or fluoride, and cations such as zinc or magnesium. Tooth mineral may also contain non-apatitic mineral phases such as octacalcium phosphate and calcium carbonate.
Tooth loss may occur as a result of dental caries, which is a multifactorial disease where bacterial acids such as lactic acid produce sub-surface demineralisation that does not fully remineralise, resulting in progressive tissue loss and eventually cavity formation. The presence of a plaque biofilm is a prerequisite for dental caries, and acidogenic bacteria such as Streptococcus mutans, may become pathogenic when levels of easily fermentable carbohydrate, such as sucrose, are elevated for extended periods of time.
Even in the absence of disease, loss of dental hard tissues can occur as a result of acid erosion and/or physical tooth wear; these processes are believed to act synergistically. Exposure of the dental hard tissues to acid causes demineralisation, resulting in surface softening and a decrease in mineral density. Under normal physiological conditions, demineralised tissues self-repair through the remineralising effects of saliva. Saliva is supersaturated with respect to calcium and phosphate, and in healthy individuals saliva secretion serves to wash out the acid challenge, and raises the pH so as to alter the equilibrium in favour of mineral deposition.
Dental erosion (i.e. acid erosion or acid wear) is a surface phenomenon that involves demineralisation, and ultimately complete dissolution of the tooth surface by acids that are not of bacterial origin. Most commonly the acid will be of dietary origin, such as citric acid from fruit or carbonated drinks, phosphoric acid from cola drinks and acetic acid such as from vinaigrette. Dental erosion may also be caused by repeated contact with hydrochloric acid (HCl) produced in the stomach, which may enter the oral cavity through an involuntary response such as gastroesophageal reflux, or through an induced response as may be encountered in sufferers of bulimia.
Tooth wear (ie physical tooth wear) is caused by attrition and/or abrasion. Attrition occurs when tooth surfaces rub against each other, a form of two-body wear. An often dramatic example is that observed in subjects with bruxism, a grinding habit where the applied forces are high, and is characterised by accelerated wear, particularly on the occlusal surfaces. Abrasion typically occurs as a result of three-body wear and the most common example is that associated with brushing with a toothpaste. In the case of fully mineralised enamel, levels of wear caused by commercially available toothpastes are minimal and of little or no clinical consequence. However, if enamel has been demineralised and softened by exposure to an erosive challenge, the enamel becomes more susceptible to tooth wear. Dentine is much softer than enamel and consequently is more susceptible to wear. Subjects with exposed dentine should avoid the use of highly abrasive toothpastes, such as those based on alumina. Again, softening of dentine by an erosive challenge will increase susceptibility of the tissue to wear.
Dentine is a vital tissue that in vivo is normally covered by enamel or cementum depending on the location i.e. crown versus root respectively. Dentine has a much higher organic content than enamel and its structure is characterised by the presence of fluid-filled tubules that run from the surface of the dentine-enamel or dentine-cementum junction to the odontoblast/pulp interface. It is widely accepted that the origins of dentine hypersensitivity relate to changes in fluid flow in exposed tubules, (the hydrodynamic theory), that result in stimulation of mechanoreceptors thought to be located close to the odontoblast/pulp interface. Not all exposed dentine is sensitive since it is generally covered with a smear layer; an occlusive mixture comprised predominantly of mineral and proteins derived from dentine itself, but also containing organic components from saliva. Over time, the lumen of the tubule may become progressively occluded with mineralised tissue. The formation of reparative dentine in response to trauma or chemical irritation of the pulp is also well documented. Nonetheless, an erosive challenge can remove the smear layer and tubule “plugs” causing outward dentinal fluid flow, making the dentine much more susceptible to external stimuli such as hot, cold and pressure. As previously indicated, an erosive challenge can also make the dentine surface much more susceptible to wear. In addition, dentine hypersensitivity worsens as the diameter of the exposed tubules increases, and since the tubule diameter increases as one proceeds in the direction of the odontoblast/pulp interface, progressive dentine wear can result in an increase in hypersensitivity, especially in cases where dentine wear is rapid.
Loss of the protective enamel layer through erosion and/or acid-mediated wear will expose the underlying dentine, and are therefore primary aetiological factors in the development of dentine hypersensitivity.
It has been claimed that an increased intake of dietary acids, and a move away from formalised meal times, has been accompanied by a rise in the incidence of dental erosion and tooth wear. In view of this, oral care compositions which help prevent dental erosion and tooth wear would be advantageous.
The present invention is based on the discovery that the presence of a triple polymer system consisting of xanthan gum, carboxymethyl cellulose and copovidone in an oral care composition comprising a source of fluoride ions enhances the efficacy of the fluoride ions in combating dental erosion.
Oral compositions comprising such a triple polymer system are described in WO 2006/013081, (Glaxo Group Ltd) for use in the treatment or alleviation of the symptoms of dry mouth by lubricating and hydrating the oral cavity. Such compositions may contain a source of fluoride ions as an anti-caries agent. There is no suggestion that such compositions can combat dental erosion or that the triple polymer system can enhance the efficacy of fluoride ions in combating dental erosion.
Van der Reijden et al (Caries Res., 1997, 31, 216-23) describes a range of in vitro experiments with saliva substitute compositions containing thickening agents to investigate their caries-protective properties, including the effect on demineralisation and remineralisation of enamel in vitro. The effect of a range of polymer materials on dissolution of hydroxyapatite crystals in 50, mM acetic acid at pH 5.0,, and a pH cycling experiment in which bovine enamel is exposed to demineralisation buffer (pH 4.8) and to remineralisation buffer (pH 7.0) containing a range of dissolved polymers, are described.
These experiments suggest that some polymers including xanthan gum and carboxymethylcellulose can reduce the demineralization of enamel in vitro and it is suggested that this may result from the formation of an adsorbed polymer layer on the enamel surface providing protection against acidic attacks.
WO 00/13531, (SmithKline Beecham) describes the use of various viscosity modifying polymer materials as tooth erosion inhibitors in acidic compositions for oral administration such as acidic beverages or acidic oral health care compositions. Examples of polymers include xanthan gum, carboxymethylcellulose and polyvinylpyrrolidone.
The role of certain polymer materials in protecting against dental erosion is described in WO 2004/054529, (Procter & Gamble) which claims a method of protecting against dental erosion comprising administering an oral care composition comprising a polymeric mineral surface active agent (ie a polyelectrolyte such as a polyphosphate, a polycarboxylate or certain carboxy-substituted polymers), wherein the polymeric mineral surface active agent is substantive to teeth and deposits a layer that protects teeth from erosive damage immediately after use and for at least one hour thereafter. It is suggested that such oral care compositions may optionally comprise a source of fluoride ions, although there is no teaching that the presence of a polymeric mineral surface active agent may enhance the efficacy of fluoride ions in protecting against dental erosion. It is also suggested that such oral compositions may comprise various thickening agents including xanthan gum and carboxymethyl cellulose. There is no suggestion that such thickening agents are substantive to teeth or can protect teeth against dental erosion.
Schaad et al (Colloids and Surfaces A: Physiochemical and Engineering Aspects 1994; 83; 285-292) describes the inhibition of dissolution of hydroxyapatite powder by adsorbed anionic polymers and suggests that some of these may be powerful agents for preventing the dissolution of enamel or bone tissues.
EP-A-691124, (Sara Lee) describes oral care products comprising a copolymer of N-vinylpyrrolidone and acrylic acid, said to result in enhanced enamel fluoride uptake in the tooth enamel. On page 11, the relative enamel fluoride uptake efficacy of various formulations containing different thickening agents is described, which thickening agents include carboxymethylcellulose, a combination of xanthan gum and a carbopol, a combination of xanthan gum and a copolymer of N-vinylpyrrolidone and acrylic acid and a combination of xanthan gum and a copolymer of a methylvinyl ether and maleic acid or anhydride.
French Patent No. 2755010, (Sara Lee) describes an oral care product containing fluoride comprising a combination of xanthan gum and a carboxylated vinyl polymer which combination is stated to enhance the efficacy of the fluoride in combating dental decay.